Schizophrenia spectrum disorders are psychiatric conditions that express by a wide range of symptoms. Current treatments are effective in controlling so-called positive symptoms (e.g., delusions or hallucinations) but are often less effective for negative symptoms (e.g., blunted affect and passive social withdrawal) as well as for cognitive impairments. Further, current anti-psychotics may induce several side-effects that limit use and patient adherence. Therefore, mechanistically novel anti-psychotics are urgently needed. Cannabidiol, a major cannabinoid of Cannabis sativa, has been investigated in both animal models for aspects of schizophrenia, clinical studies, and controlled trials. Animal studies have raised substantial evidence for cannabidiol’s anti-psychotic effects. While controlled clinical trials have shown mixed results, studies using cannabidiol at higher dosages have demonstrated its ability to ameliorate psychotic symptoms while showing a relatively benign side-effect profile. Although the currently available data is short of any proof justifying the registration of cannabidiol as an anti-psychotic at present, the data from phase II clinical trials justify further study of cannabidiol’s antipsychotic properties in controlled clinical trials to clarify its therapeutic value and safety profile, notably in long-term treatment. In addition, more insight into its mechanisms of action may broaden our understanding of new targets for treatment.